Background: Sepsis in children is a conundrum of diagnostic and therapeutic challenges. There is an exigent need for a novel biomarker that can serve as a clear distinguisher of sepsis from other non-septic inflammatory conditions. The role of presepsin as a biomarker of sepsis in children is still a matter of scientific inquiry. Aim and objectives: To evaluate the diagnostic accuracy of presepsin for the prediction of septic shock, in children aged 1 month to 18 years. Materials and methods: This prospective cohort study was conducted in the pediatric emergency, ward, and intensive care unit of a tertiary care hospital. We enrolled all consecutive admissions aged 1 month to 18 years with a diagnosis of sepsis and compared the presepsin, procalcitonin, and C-reactive protein (CRP) levels on admission (day 1) and 72 hours later (day 4) with the clinical outcomes. Results: The mean (±SD) presepsin values in blood culture-proven sepsis patients at admission and 72 hours later were 609.77 ± 417.30 and 839 ± 748.07, respectively. The procalcitonin and presepsin levels at 72 hours in sepsis patients with shock were significantly elevated (38.2 ± 45.55 and 1129.1 ± 1133.80, respectively) as compared to those without shock (10.7 ± 25.42 and 472.5 ± 507.81, respectively), p <0.05. The receiver operating characteristic (ROC) curve analysis of presepsin at 72 hours had an area under curve (AUC) of 0.730, suggesting a fair diagnostic accuracy. Conclusion: Elevated presepsin levels may indicate greater severity of sepsis, particularly in those with shock. However, it lacks diagnostic ability early in the disease and has limited prognostic potential in predicting mortality.